Sunday, October 28, 2012

One cannot evaluate these claims without virtually redoing their literature survey but I would be surprised if the evidence was anything other than epidemiological -- and people who are already in poor health are probably more likely to be depressed -- thus accounting for the results

Thousands of women who take anti-depressants during pregnancy are endangering their unborn babies, researchers have warned.

The widely prescribed pills have been found drastically to raise the odds of miscarriages, premature birth, autism and life-threatening high blood pressure, they say.

Harvard researchers believe far too many women are taking the drugs during pregnancy because their GPs are not aware of the dangers.

They also suspect that drug companies are trying to play down the risks because anti-depressants are so lucrative to them.

They focused on the complications linked to a group of drugs called selective serotonin reuptake inhibitors (SSRIs), which include Prozac and Seroxat. Between 2 and 3 per cent of pregnant women in the UK are thought to be on these drugs – up to 19,500 every year.

But the researchers have found that they increase the risk of a miscarriage by 17 per cent and more than double the likelihood of pre-eclampsia – high blood pressure during pregnancy – which can be fatal.

They also double the chances of the baby being born premature, or developing autism. In addition, the researchers say, the babies are more likely to suffer from heart defects and problems with their bowels.

SSRIs treat depression by boosting the level of the ‘happy hormone’ serotonin in the brain. But the researchers believe that serotonin is also getting into the womb and harming the development of the foetus’s brain, lungs, heart and digestive system.

Dr Adam Urato, assistant professor of obstetrics and gynaecology at Tufts University School of Medicine, in Boston, who was involved in the study, said: ‘I am absolutely concerned – very concerned.

‘We are witnessing a large-scale human experiment. Never before have we chemically altered human foetal development on such a large scale. 'And my concern is why I am trying to get the word out to patients, health care providers, and the public.’

She said GPs were handing out prescriptions for the drugs even though depression could be far better treated through exercise, talking therapies and even yoga.

‘These are probably not particularly safe medicines to take during pregnancy,’ she said. ‘We’re not saying that every pregnant woman should go off her medication. 'Obviously you don’t want a pregnant woman to attempt suicide.’

The researchers, who presented their findings to the annual conference of the American Society for Reproductive Medicine in San Diego, California, have analysed more than 100 existing studies looking at the risks of SSRIs.

Their findings are due to be published next week in the respected journal Human Reproduction.

The researchers say that if women take the pills when they are trying for a baby but come off as soon as they find out they are pregnant, it may be too late.

Dr Urato added: ‘Many of the experts in this area receive funding from the anti-depressant majors. These experts continue to downplay the risks of these agents and to promote the benefits of their use in pregnancy.’

A spokesman for the Association of the British Pharmaceutical Industry said: ‘Clinical decisions about the treatment of depression are complex and must be made by clinicians in consultation with individual patients, regardless of whether or not they are pregnant.’

A statistical analysis finds that study results showing a 'very large effect' rarely hold up when other researchers try to replicate them

Given the excruciatingly bad methodology and childish logic of so many published studies, this should be no surprise at all

If a medical study seems too good to be true, it probably is, according to a new analysis.

In a statistical analysis of nearly 230,000 trials compiled from a variety of disciplines, study results that claimed a "very large effect" rarely held up when other research teams tried to replicate them, researchers reported in Wednesday's edition of the Journal of the American Medical Assn.

"The effects largely go away; they become much smaller," said Dr. John Ioannidis, the Stanford University researcher who was the report's senior author. "It's likely that most interventions that are effective have modest effects."

Ioannidis and his colleagues came to this conclusion after examining 228,220 trials grouped into more than 85,000 "topics" — collections of studies that paired a single medical intervention (such as taking a non-steroidal anti-inflammatory drug for postoperative pain) with a single outcome (such as experiencing 50% relief over six hours). In 16% of those topics, at least one study in the group claimed that the intervention made patients at least five times more likely to either benefit or suffer compared with control patients who did not receive the treatment.

In at least 90% of those cases, the team found, including data from subsequent trials reduced those odds.

The analysis revealed several reasons to question the significance of the very-large-effect studies, Ioannidis said.

Studies that reported striking results were more likely to be small, with fewer than 100 subjects who experienced fewer than 20 medical events. With such small sample sizes, Ioannidis said, large effects are more likely to be the result of chance.

"Trials need to be of a magnitude that can give useful information," he said.

What's more, the studies that claimed a very large effect tended to measure intermediate effects — for example, whether patients who took a statin drug reduced their levels of bad cholesterol in their blood — rather than incidence of disease or death itself, outcomes that are more meaningful in assessing medical treatments.

The analysis did not examine individual study characteristics, such as whether the experimental methods were flawed.

The report should remind patients, physicians and policymakers not to give too much credence to small, early studies that show huge treatment effects, Ioannidis said.

One such example: the cancer drug Avastin. Clinical trials suggested the drug might double the time breast cancer patients could live with their disease without getting worse. But follow-up studies found no improvements in progression-free survival, overall survival or patients' quality of life. As a result, the U.S. Food and Drug Administration in 2011 withdrew its approval to use the drug to treat breast cancer, though it is still approved to treat several other types of cancer.

With early glowing reports, Ioannidis said, "one should be cautious and wait for a better trial."

Dr. Rita Redberg, a cardiologist at UC San Francisco who was not involved in the study, said devices and drugs frequently get accelerated approval on the basis of small studies that use intermediate end points. "Perhaps we don't need to be in such a rush to approve them," she said.

The notion that dramatic results don't hold up under closer scrutiny isn't new. Ioannidis, a well-known critic of the methods used in medical research, has written for years about the ways studies published in peer-reviewed journals fall short. (He's perhaps best known for a 2005 essay in the journal PLoS Medicine titled, "Why Most Published Research Findings Are False.")

But the scope of the JAMA analysis sets it apart from Ioannidis' earlier efforts, said Dr. Gordon Guyatt, a clinical epidemiologist at McMaster University in Hamilton, Canada, who was not involved in the work. "They looked through a lot of stuff," he said.

Despite widespread recognition that big effects are likely to disappear upon further scrutiny, people still "get excited, and misguidedly so" when presented with home-run results, Guyatt said.

He emphasized that modest effects could benefit patients and were often "very important" on a cumulative basis.

Where it is not bunk is when it shows that some treatment or influence has no effect on lifespan or disease incidence. It is as convincing as disproof as it is unconvincing as proof. Think about it. As Einstein said: No amount of experimentation can ever prove me right; a single experiment can prove me wrong.

Epidemiological studies are useful for hypothesis-generating or for hypothesis-testing of theories already examined in experimental work but they do not enable causative inferences by themselves

The standard of reasoning that one commonly finds in epidemiological journal articles is akin to the following false syllogism:
Chairs have legs
You have legs
So therefore you are a chair

I am rather in despair that important medical research is plagued by arrant nonsense. The simple truth that correlation is not causation seems unknown to most medical writers. As a last ditch attempt to get that truth into a few more skulls let me be "offensive". Offensiveness may serve to get the matter noticed. So here is the story: There is about a -.5 correlation between lip size and IQ. Big lips predict low IQ. Your run-of-the mill medical researcher will pounce on that as a huge breakthrough in finding the causes of IQ -- and propound new theories about things such as blood circulation to explain how lips affect IQ. But that is nonsense. Big lips are mostly found on people of African ancestry and, as all the studies attest, Africans are a very low IQ group. The correlation arises because of heredity, not lip size. There is a third factor behind the correlation -- and the possibility of such third factors seems to be a jaw-dropping surprise to most medical researchers

SALT -- SALT -- SALT

1). A good example of an epidemiological disproof concerns the dreaded salt (NaCl). We are constantly told that we eat too much salt for good health and must cut back our consumption of it. Yet there is one nation that consumes huge amounts of salt. So do they all die young there? Quite the reverse: Japan has the world's highest concentration of centenarians. Taste Japan's favourite sauce -- soy sauce -- if you want to understand Japanese salt consumption. It's almost solid salt.

2). We need a daily salt intake to counter salt-loss through perspiration and the research shows that people on salt-restricted diets die SOONER. So the conventional wisdom is not only wrong. It is positively harmful

3). Table salt is a major source of iodine, which is why salt is normally "iodized" by official decree. Cutting back salt consumption runs the risk of iodine deficiency, with its huge adverse health impacts -- goiter, mental retardation etc. GIVE YOUR BABY PLENTY OF SALTY FOODS -- unless you want to turn it into a cretin

4). Our blood has roughly the same concentration of salt as sea-water so claims that the body cannot handle high levels of salt were always absurd

5). The latest academic study shows that LOW salt in your blood is most likely to lead to heart attacks. See JAMA. 2011;305(17):1777-1785. More here and here and here for similar findings. Salt is harmless but a deficiency of it is not. We need it. See also here

PEANUTS: There is a vaccination against peanut allergy -- peanuts themselves. Give peanut products (e.g. peanut butter -- or the original "Bamba" if you have Israeli contacts) to your baby as soon as it begins to take solid foods and that should immunize it for life. See here and here (scroll down). It's also likely that a mother who eats peanuts while she is lactating may confer some protection on her baby. See here

THE SIDE-EFFECT MANIA. If a drug is shown to have troublesome side-effects, there are always calls for it to be banned or not authorized for use in the first place. But that is insane. ALL drugs have side effects. Even aspirin causes stomach bleeding, for instance -- and paracetamol (acetaminophen) can wreck your liver. If a drug has no side effects, it will have no main effects either. If you want a side-effect-free drug, take a homeopathic remedy. They're just water.

Although I am an atheist, I have never wavered from my view that the New Testament is the best guide to living and I still enjoy reading it. Here is what the apostle Paul says about vegetarians: "For one believeth that he may eat all things: another, who is weak, eateth herbs. Let not him that eateth despise him that eateth not; and let not him which eateth not judge him that eateth." (Romans 14: 2.3). What perfect advice! That is real tolerance: Very different from the dogmatism of the food freaks. Interesting that vegetarianism is such an old compulsion, though.

Even if we concede that getting fat shortens your life, what right has anybody got to question someone's decision to accept that tradeoff for themselves? Such a decision could be just one version of the old idea that it is best to have a short life but a merry one. Even the Bible is supportive of that thinking. See Ecclesiastes 8:15 and Isaiah 22: 13. To deny the right to make such a personal decision is plainly Fascistic.

Obesity does NOT causes diabetes. But insatiable eating is a prominent symptom of diabetes. So diabetes DOES cause obesity, which accounts for the correlation between the two things. The streets are full of fatties who don't have diabetes. How come? If conventional medical theory were correct we should be in the midst of an epidemic of diabetes. A recent high quality study has also found that fatties are LESS likely to die of diabetes

Elite people frequently express disapproval of red meat eating as a way of expressing their felt superiority to the ordinary people who eat it

IQ: Political correctness makes IQ generally unmentionable so it is rarely controlled for in epidemiological studies. This is extremely regrettable as it tends to vitiate findings that do not control for it. When it is examined, it is routinely found to have pervasive effects. We read, for instance, that "The mother's IQ was more highly predictive of breastfeeding status than were her race, education, age, poverty status, smoking, the home environment, or the child's birth weight or birth order". So political correctness can render otherwise interesting findings moot

"To kill an error is as good a service as, and sometimes better than, the establishing of a new truth or fact" -- Charles Darwin

"Most men die of their remedies, not of their diseases", said Moliere. That may no longer be true in general but there is still a lot of false medical "wisdom" around that does harm to various degrees -- the statin and antioxidant fads, for instance. And showing its falsity is rarely the problem. The problem is getting people -- medical researchers in particular -- to abandon their preconceptions

Bertrand Russell could have been talking about today's conventional dietary "wisdom" when he said: "The fact that an opinion has been widely held is no evidence whatever that it is not utterly absurd; indeed in view of the silliness of the majority of mankind, a widespread belief is more likely to be foolish than sensible.”

The challenge, as John Maynard Keynes knew, "lies not so much in developing new ideas as in escaping from old ones".

"Obesity" is 77% genetic. So trying to make fatties slim is punishing them for the way they were born. That sort of thing is furiously condemned in relation to homosexuals so why is it OK for fatties?

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Some more problems with the "Obesity" war:

1). It tries to impose behavior change on everybody -- when most of those targeted are not obese and hence have no reason to change their behaviour. It is a form of punishing the innocent and the guilty alike. (It is also typical of Leftist thinking: Scorning the individual and capable of dealing with large groups only).

2). The longevity research all leads to the conclusion that it is people of MIDDLING weight who live longest -- not slim people. So the "epidemic" of obesity is in fact largely an "epidemic" of living longer.

3). It is total calorie intake that makes you fat -- not where you get your calories. Policies that attack only the source of the calories (e.g. "junk food") without addressing total calorie intake are hence pissing into the wind. People involuntarily deprived of their preferred calorie intake from one source are highly likely to seek and find their calories elsewhere.

4). So-called junk food is perfectly nutritious. A big Mac meal comprises meat, bread, salad and potatoes -- which is a mainstream Western diet. If that is bad then we are all in big trouble.

5). Food warriors demonize dietary fat. But Eskimos living on their traditional diet eat huge amounts of fat with no apparent ill-effects. At any given age they in fact have an exceptionally LOW incidence of cardiovascular disease. And the average home-cooked roast dinner has LOTS of fat. Will we ban roast dinners?

6). The foods restricted are often no more calorific than those permitted -- such as milk and fruit-juice drinks.

7). Tendency to weight is mostly genetic and is therefore not readily susceptible to voluntary behaviour change.

8). And when are we going to ban cheese? Cheese is a concentrated calorie bomb and has lots of that wicked animal fat in it too. Wouldn't we all be better off without it? And what about butter and margarine? They are just about pure fat. Surely they should be treated as contraband in kids' lunchboxes! [/sarcasm].

9). And how odd it is that we never hear of the huge American study which showed that women who eat lots of veggies have an INCREASED risk of stomach cancer? So the official recommendation to eat five lots of veggies every day might just be creating lots of cancer for the future! It's as plausible (i.e. not very) as all the other dietary "wisdom" we read about fat etc.

10). And will "this generation of Western children be the first in history to lead shorter lives than their parents did"? This is another anti-fat scare that emanates from a much-cited editorial in a prominent medical journal that said so. Yet this editorial offered no statistical basis for its opinion -- an opinion that flies directly in the face of the available evidence.

11). A major cause of increasing obesity is certainly the campaign against it -- as dieting usually makes people FATTER. If there were any sincerity to the obesity warriors, they would ban all diet advertising and otherwise shut up about it. Re-authorizing now-banned school playground activities and school outings would help too. But it is so much easier to blame obesity on the evil "multinationals" than it is to blame it on your own restrictions on the natural activities of kids

12. Fascism: "What we should be doing is monitoring children from birth so we can detect any deviations from the norm at an early stage and action can be taken". Who said that? Joe Stalin? Adolf Hitler? Orwell's "Big Brother"? The Spanish Inquisition? Generalissimo Francisco Franco Bahamonde? None of those. It was Dr Colin Waine, chairman of Britain's National Obesity Forum. What a fine fellow!

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Trans fats: For one summary of the weak science behind the "trans-fat" hysteria, see here. Trans fats have only a temporary effect on blood chemistry and the evidence of lasting harm from them is dubious. By taking extreme groups in trans fats intake, some weak association with coronary heart disease has at times been shown in some sub-populations but extreme group studies are inherently at risk of confounding with other factors and are intrinsically of little interest to the average person.

The "antioxidant" religion: The experimental evidence is that antioxidants SHORTEN your life, if anything. Studies here and here and here and here and here and here and here and here, for instance. That they are of benefit is a great theory but it is one that has been coshed by reality plenty of times.

The medical consensus is often wrong. The best known wrongheaded medical orthodoxy is that stomach ulcers could not be caused by bacteria because the stomach is so acidic. Disproof of that view first appeared in 1875 (Yes. 1875) but the falsity of the view was not widely recognized until 1990. Only heroic efforts finally overturned the consensus and led to a cure for stomach ulcers. See
here and here and here.

Dieticians are just modern-day witch-doctors. There is no undergirding in double-blind studies for their usual recommendations

The fragility of current medical wisdom: Would you believe that even Old Testament wisdom can sometimes trump medical wisdom? Note this quote: "Spiess discussed Swedish research on cardiac patients that compared Jehovah's Witnesses who refused blood transfusions to patients with similar disease progression during open-heart surgery. The research found those who refused transfusions had noticeably better survival rates.

Medical wisdom can in fact fly in the face of the known facts. How often do we hear reverent praise for the Mediterranean diet? Yet both Australians and Japanese live longer than Greeks and Italians, despite having very different diets. The traditional Australian diet is in fact about as opposite to the Mediterranean diet as you can get. The reverence for the Mediterranean diet can only be understood therefore as some sort of Anglo-Saxon cultural cringe. It is quite brainless. Why are not the Australian and Japanese diets extolled if health is the matter at issue?

Since many of my posts here make severe criticisms of medical research, I should perhaps point out that I am also a severe critic of much research in my own field of psychology. See here and here

This is NOT an "alternative medicine" site. Perhaps the only (weak) excuse for the poorly substantiated claims that often appear in the medical literature is the even poorer level of substantiation offered in the "alternative" literature.

I used to teach social statistics in a major Australian university and I find medical statistics pretty obfuscatory. They seem uniformly designed to make mountains out of molehills. Many times in the academic literature I have excoriated my colleagues in psychology and sociology for going ga-ga over very weak correlations but what I find in the medical literature makes the findings in the social sciences look positively muscular. In fact, medical findings are almost never reported as correlations -- because to do so would exhibit how laughably trivial they generally are. If (say) 3 individuals in a thousand in a control group had some sort of an adverse outcome versus 4 out of a thousand in a group undergoing some treatment, the difference will be published in the medical literature with great excitement and intimations of its importance. In fact, of course, such small differences are almost certainly random noise and are in any rational calculus unimportant. And statistical significance is little help in determining the importance of a finding. Statistical significance simply tells you that the result was unlikely to be an effect of small sample size. But a statistically significant difference could have been due to any number of other randomly-present factors.

"The modern literature on hate crimes began with a remarkable 1933 book by Arthur Raper titled The Tragedy of Lynching. Raper assembled data on the number of lynchings each year in the South and on the price of an acre's yield of cotton. He calculated the correlation coefficient between the two series at -0.532. In other words, when the economy was doing well, the number of lynchings was lower.... In 2001, Donald Green, Laurence McFalls, and Jennifer Smith published a paper that demolished the alleged connection between economic conditions and lynchings in Raper's data. Raper had the misfortune of stopping his analysis in 1929. After the Great Depression hit, the price of cotton plummeted and economic conditions deteriorated, yet lynchings continued to fall. The correlation disappeared altogether when more years of data were added."

So we must be sure to base our conclusions on ALL the data. But in medical research, data selectivity and the "overlooking" of discordant research findings is epidemic.

The Truth About Ancel Keys. Keys was a brilliant man but his concentration on heart disease misled him. He was right that high fat intake predicted high rates of heart disease (though it was ANIMAL fat in particular that was the "culprit") but he overlooked that the same intake predicted LESS mortality from other causes. The same narrow vision led him to be the earliest prominent advocate of the "Mediterranean diet" hypothesis. It's true that Mediterraneans have less heart disease but they have more of other causes of death, so that Mediterranean countries do not have particularly long lifespans when compared with other developed countries. If there are any lessons about diet to be learned from lifespans, it is un-Mediterranean countries like Australia and the Nordic countries that one should look to.

The intellectual Roman Emperor Marcus Aurelius (AD 121-180) could have been speaking of the prevailing health "wisdom" of today when he said: "The object in life is not to be on the side of the majority, but to escape finding oneself in the ranks of the insane."

Improbable events do happen at random -- as mathematician John Brignell notes rather tartly: "Consider, instead, my experiences in the village pub swindle. It is based on the weekly bonus ball in the National Lottery. It so happens that my birth date is 13, so that is the number I always choose. With a few occasional absences abroad I have paid my pound every week for a year and a half, but have never won. Some of my neighbours win frequently; one in three consecutive weeks. Furthermore, I always put in a pound for my wife for her birth date, which is 11. She has never won either. The probability of neither of these numbers coming up in that period is less than 5%, which for an epidemiologist is significant enough to publish a paper.

Kids are not shy anymore. They are "autistic". Autism is a real problem but the rise in its incidence seems likely to be the product of overdiagnosis -- the now common tendency to medicalize almost all problems.

One of the great pleasures in life is the first mouthful of cold beer on a hot day -- and the food Puritans can stick that wherever they like

NOTE: The archives provided by blogspot below are rather inconvenient. They break each month up into small bits. If you want to scan whole months at a time, the backup archives will suit better. See here or here